Study links ketamine and psychedelics to immune signaling pathways that may drive rapid antidepressant effects

New research suggests that ketamine and classic psychedelics may produce rapid antidepressant effects through convergent immune signaling pathways, despite acting on different brain receptors. In lab-grown human brain cells and spinal fluid data, researchers identified 103 proteins altered by ketamine and at least one other tested drug, with 86% also affected by psychedelics. The strongest shared network centered on immune molecules including interleukin-15 and monocyte chemoattractant protein-1, alongside a secondary module involving insulin signaling and neural rewiring. In a clinical trial of 39 people with treatment-resistant depression and 25 healthy volunteers, immune activity patterns shifted after ketamine, and specific cytokine ratios predicted treatment response. The findings are exploratory, limited by small samples, female-only cell donors, healthy spinal-fluid donors, and mismatched measurement timing. Larger studies are needed to confirm whether these pathways can guide treatment or enable safer rapid-acting therapies.